Funding is requested for a 500 MHz NMR spectrometer to replace a 15 year old, outdated 500 MHz NMR. The new instrument is necessary for the solution-state NMR needs of the NIH user group at Columbia University that consists of 10 faculty who in aggregate are funded by 16 NIH grants. NMR is a key tool for all the investigators and the resolution and dispersion of a 500 MHz magnet is necessary for the complex molecules under study. To provide maximum flexibility and accommodate the diverse needs of the user group, two probes and three radio frequency channels are requested. A triple-resonance microprobe will provide high mass sensitivity at low cost and a broadband probe will allow detection of nuclei other than proton including fluorine. The acquisition of a new 500 MHz NMR will directly support research that will have a clear impact on human health including the design and synthesis of new therapeutics, the identification and characterization of new therapeutic targets, and the development of new medical diagnostics including DNA sequencing methods. Among the disease states targeted are neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's, various heritable diseases, and cancer.